Genetic Variant BLM:c.4077-59_4077-57dupAAG (chr15-90815041-G-GGAA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000057.4(BLM):c.4077-59_4077-57dupAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,533,884 control chromosomes in the GnomAD database, including 308,944 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31223 hom., cov: 0)

Exomes 𝑓: 0.63 ( 277721 hom. )

Consequence

BLM
NM_000057.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.130

Publications

4 publications found

Variant links:

Genes affected

BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]

BLM Gene-Disease associations (from GenCC):

Bloom syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet, Genomics England PanelApp, ClinGen
osteosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

BLM links:

ENSG00000287061 (HGNC:):

ENSG00000287061 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 15-90815041-G-GGAA is Benign according to our data. Variant chr15-90815041-G-GGAA is described in ClinVar as [Likely_benign]. Clinvar id is 210530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLM	NM_000057.4 link	c.4077-59_4077-57dupAAG		intron_variant	Intron 21 of 21	ENST00000355112.8	NP_000048.1	P54132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8 link	c.4077-59_4077-57dupAAG		intron_variant	Intron 21 of 21	1	NM_000057.4	ENSP00000347232.3		P54132

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

96752

AN:

151496

Hom.:

31190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.587

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.636

GnomAD4 exome

AF:

0.631

AC:

871868

AN:

1382270

Hom.:

277721

AF XY:

0.629

AC XY:

435241

AN XY:

692044

show subpopulations

African (AFR)

AF:

0.627

AC:

20027

AN:

31940

American (AMR)

AF:

0.769

AC:

34111

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

17352

AN:

25672

East Asian (EAS)

AF:

0.803

AC:

31521

AN:

39276

South Asian (SAS)

AF:

0.610

AC:

51450

AN:

84276

European-Finnish (FIN)

AF:

0.586

AC:

26458

AN:

45144

Middle Eastern (MID)

AF:

0.630

AC:

3552

AN:

5642

European-Non Finnish (NFE)

AF:

0.621

AC:

650618

AN:

1048076

Other (OTH)

AF:

0.636

AC:

36779

AN:

57858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

15793

31586

47379

63172

78965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.639

AC:

96844

AN:

151614

Hom.:

31223

Cov.:

AF XY:

0.638

AC XY:

47283

AN XY:

74054

show subpopulations

African (AFR)

AF:

0.615

AC:

25412

AN:

41318

American (AMR)

AF:

0.718

AC:

10951

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.681

AC:

2359

AN:

3464

East Asian (EAS)

AF:

0.813

AC:

4171

AN:

5132

South Asian (SAS)

AF:

0.615

AC:

2963

AN:

4814

European-Finnish (FIN)

AF:

0.587

AC:

6144

AN:

10472

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.629

AC:

42659

AN:

67870

Other (OTH)

AF:

0.638

AC:

1342

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1755

3510

5266

7021

8776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.644

Hom.:

3360

Asia WGS

AF:

0.700

AC:

2435

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 29, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bloom syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr15-90815041-G-GGAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over